Cytomegalovirus (CMV) is the most common recognized cause of viral-induced psychomotor retardation. As many as 5000 infants are born in the U.S. each year with neurologic, psychomotor, perceptual, or behavioral abnormalities due to CMV. We have found and others have confirmed that infants with active CMV infections have a defect in CMV specific cell-mediated immunity (CMI) that can be detected by a lymphocyte proliferation assay. We plan to continue our longitudinal virologic and immunologic studies to determine if this defect in CMI is responsible for ongoing viral replication with potential organ destruction. We have determined that the vast majority of infants, whether they have cytomegalic inclusion disease, late intrauterine infection, or perinatally acquired CMV have this defect. We plan to further investigate the role of cellular immunity as a host defense against CMV by studying direct and antibody dependent cellular cytotoxicity as well as proliferative responses to CMV antigen in infants with active infection. In an open study of 7 infants we found that transfer factor (TF) was associated with a significant increase in lymphocyte proliferation to CMV antigen and a diminution or cessation of viruria. We plan to continue these preliminary studies by adding 3 more infants treated with a pool of TF made from 3 CMV-immune donors. If results in these 3 infants confirm our findings in the first 7 treated with single-donor TF, we plan to launch a randomized, placebo-controlled trial of TF for treatment of congenital and perinatal CMV.